1. Field of the Invention
This invention relates to novel pyrido[2,3-f][1,4]-thiazepines and novel pyrido[3,2-b][1,5]benzothiazepines. These compounds are inhibitors of calcium ion uptake into smooth muscle tissue, and act to relax or prevent contraction of the tissue mediated by calcium mechanisms. The compounds are active antihypertensives and bronchodilators.
These compounds are useful for the treatment of cardiovascular disorders, including hypertension, ischemia, angina, congestive heart failure, migraine, myocardial infarction and stroke. The compounds are also useful for the treatment of other disorders such as hypersensitivity, allergy, asthma, dysmenorrhea, esophageal spasm, gastrointestinal motility disorders, glaucoma, premature labor and urinary tract disorders. The present invention also relates to a process for preparing these compounds, compositions thereof, methods of use and novel intermediates.
2. Related Disclosure
U.S. Pat. No. 4,285,955 and U.S. Pat. No. 4,483,985 (which is a divisional of the aforementioned patent) disclose acyclic sulfone substitution on simple dihydropyridines which possess calcium channel antagonist activity. However, the compounds in question are chemically distinct from the compounds of the present invention.
10-Phenyl-2H-thiopyranol[3,2-b]quinolines are disclosed in Pagani, G.P.A., J. Chem. Soc.. Perkin Trans. 2, 1392 (1974). However, these compounds are not calcium channel antagonists.
U.S. Pat. No. 4,532,248 discloses a broad genus of dihydropyridines, including cyclic sulfones fused to a dihydropyridine nucleus. Cardiotonic activity is claimed for the entire genus. The compounds of the present invention, on the other hand, are potent calcium antagonists with pharmacologic activity opposite to that claimed in U.S. Pat. No. 4,532,248.